Tatsu Miyoshi

Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis.

Adenocarcinomas with a micropapillary pattern (MPP), featuring small papillary tufts lacking a central fibrovascular core, are thought to have a poor prognosis. To examine whether the MPP is a predictor of prognosis, clinicopathologic characteristics of adenocarcinomas were analyzed with particular reference to survival of early-stage patients. The subjects were 344 consecutive patients (female/male ratio 163:181) for whom complete surgical resection was undertaken at the Cancer Institute Hospital, Japan, during 1986–1995. Histologically, they were divided into two groups: MPP-positive (n = 139; 40%) and MPP-negative (n = 205; 60%). The following items were significantly more frequent in the MPP-positive group: metastasis to lymph nodes (p <0.001), pleural invasion (p = 0.02), intrapulmonary metastasis (p <0.001), and nonsmoking status (p = 0.002). In stage I patients (i.e., without lymph node metastasis, n = 154), 5-year survival of the MPP-positive group (n = 45) was 79%, significantly lower than the MPP-negative group (n = 109) of 93% (p = 0.004). In many cases of the c-stage I MPP-positive group, upstaging was necessary on the basis of pathologic findings for metastases, and the survival was between stage I and stage II. Our study clearly indicated that the MPP is a distinct prognostic marker for lung adenocarcinoma, particularly regarding apparent stage I diseases.

Integrated classification of lung tumors and cell lines by expression profiling

The utility of cancer cell lines depends largely on their accurate classification, commonly based on histopathological diagnosis of the cancers from which they were derived. However, because cancer is often heterogeneous, the cell line, which also has the opportunity to alter in vitro, may not be representative. Yet without the overall architecture used in histopathological diagnosis of fresh samples, reclassification of cell lines has been difficult. Gene-expression profiling accurately reproduces histopathological classification and is readily applicable to cell lines. Here, we compare the gene-expression profiles of 41 cell lines with 44 tumors from lung cancer. These profiles were generated after hybridization of samples to four replicate 7,685-element cDNA microarrays. After removal of genes that were uniformly up- or down-regulated in fresh compared with cell-line samples, cluster analysis produced four major branch groups. Within these major branches, fresh tumor samples essentially clustered according to pathological type, and further subclusters were seen for both adenocarcinoma (AC) and small cell lung carcinoma (SCLC). Four of eight squamous cell carcinoma (SCC) cell lines clustered with fresh SCC, and 11 of 13 SCLC cell lines grouped with fresh SCLC. In contrast, although none of the 11 AC cell lines clustered with AC tumors, three clustered with SCC tumors and six with SCLC tumors. Although it is possible that preexisting SCC or SCLC cells are being selected from AC tumors after establishment of cell lines, we propose that, even in situ, AC will ultimately progress toward one of two poorly differentiated phenotypes with expression profiles resembling SCC or SCLC.

Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)

Aims:  A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (≤20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)‐type tumours (Noguchis type A and B) based on the absence of active fibroblastic proliferation. However, BAC‐type tumours with active fibroblastic proliferation (Noguchis type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma.

Correlation between morphology and EGFR mutations in lung adenocarcinomas Significance of the micropapillary pattern and the hobnail cell type.

The presence of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations significantly correlates with tumor sensitivity to TK inhibitors, particularly in lung adenocarcinomas, the predominant histological subtype in Japan and the United States. To clarify links between EGFR mutations and pathological findings in Japanese lung cancer, detailed pathological features of adenocarcinomas were examined using the WHO criteria as well as our cell type classification (hobnail, columnar and polygonal). Medical records were reviewed for a total of 107 surgically resected tumors. Clinicopathological factors were examined and correlations with EGFR status were evaluated. EGFR mutations were found in 63 patients (59%) distributed through all four exons examined (through exons 18-21). EGFR mutations were significantly associated with female gender (P=0.003), non-smoker status (P=0.008) and hobnail cell morphology (P<0.00001). In addition, detailed pathological examination showed significant associations with bronchioloalveolar carcinoma (BAC) component and a micropapillary pattern (MPP) (P=0.012 and 0.043, respectively). We conclude that characteristic histological features, i.e. the hobnail cell morphology and the presence of BAC component and MPP are good predictors of EGFR mutations in lung adenocarcinoma.

Human pulmonary dirofilariasis: A case report and review of the recent Japanese literature

Abstract:  Human pulmonary dirofilariasis is a rare zoonotic infection caused by the dog heartworm Dirofilaria immitis, which is transmitted via a vector/intermediate host, generally the mosquito. The authors present a case of histologically diagnosed human pulmonary dirofilariasis, in which the lesion was resected using video‐assisted thoracic surgery (VATS). The authors also review 24 cases of such zoonosis reported in Japan from 1998 to 2004. Of these 24 patients with human pulmonary dirofilariasis, 12 (50%) were men (mean age 54 years, range 29–80 years) and 67% were asymptomatic. Most patients (83%) had a solitary lung nodule, 95% of the lesions were <30 mm and 13% had a pleural effusion. VATS was performed to obtain a histopathological diagnosis in the majority (61%) of patients whom the authors reviewed. VATS would appear to be the best method for diagnosing pulmonary dirofilariasis.

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern.

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E‐cadherin‐mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E‐cadherin, α‐catenin, and β‐catenin was detected in both the micropapillary and non‐micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non‐micropapillary, area. The adhesive function of E‐cadherin depends on the integrity of the entire cadherin–catenin–actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that usually occurs in children and young adults. Anaplastic lymphoma kinase (ALK) abnormalities in IMT, determined using immunohistochemistry and/or molecular genetic studies, including fluorescence in situ hybridization (FISH), have almost been limited to children and young adults. In elderly cases of IMT, these ALK abnormalities are very rare. We report on a case of IMT arising in the posterior mediastinum of a 59-year-old Japanese man that showed ALK abnormalities determined using immunohistochemistry and FISH, suggesting the neoplastic nature of a subset of IMTs in older patients similar to those in younger ones and the presence of an additional mechanism(s) that allows them to start to grow late.

Does Pneumothorax Occurrence Correlate with a Change in the Weather

PurposeThere has been speculation that weather changes correlate with the incidence of spontaneous pneumothorax, although this has not been verified. Moreover, there are no significant data available on the meteoropathic pneumothorax in Asia. The aim of this study was to investigate the possible correlation and to compare our results to those of the United States and Europe.MethodsFrom January 2000 to December 2009, 317 spontaneous pneumothorax cases with clear dates of onset were treated in our institution. Using the meteorological data of Fukuoka, Japan, the days with and without an occurrence of pneumothorax were statistically compared in terms of atmospheric pressure, the amount of precipitation, temperature, humidity, hours of sunshine, and occurrence of a typhoon and lightning.ResultsMultivariate analysis revealed that a decrease in the hours of sunshine, an increase in mean temperatures 2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.0083, 0.0032, 0.0351, respectively). However, typhoons, as an “unusual” weather condition, did not influence the incidence of pneumothorax (P = 0.983).ConclusionsOur results show strong similarities with reports from European countries despite the different climates. We conclude that the occurrence of pneumothorax appears to correlate with some weather conditions in Japan.

Postradiation Sarcoma of the Chest Wall: Report of Two Cases

Postradiation sarcoma is a rare late complication of external radiotherapy. We herein present two cases with this disease. A 54-year-old man had undergone a lobectomy and chest wall resection for Pancoast type lung cancer 7 years previously. He had undergone irradiation with a total dose of 50 Gy. Computed tomography (CT) demonstrated a tumorous expansion of the right lateral thoracic wall. A pathological examination confirmed a diagnosis of osteosarcoma. A 60-year-old woman had undergone a resection of the lateral chest wall mass, which was diagnosed to be Hodgkins disease in 1991. Chemotherapy was given postoperatively. A tumorous lesion arose again and irradiation was performed with a total dose of 110 Gy. In 2000, two tumors appeared in the irradiation field. A pathological examination showed a sarcoma with divergent differentiation. In 2003, a tumor recurred and was diagnosed to be a liposarcoma. Patients who have received radiotherapy should therefore be followed up while taking into consideration the possible development of postradiation sarcoma.

A Case of Intraluminal Typical Bronchial Carcinoid Treated by Bronchoscopy.

背景. 気管支カルチノイドの治療は肺癌の手術に準じた外科的切除が一般的であるが, 中枢発生の腔内型定型的気管支カルチノイドに対しては, 気管支鏡下のレーザー焼灼や光線力学的治療, 凝固子等を用いた気管支鏡下切除の有用性が報告されている. 今回我々も腔内型定型的気管支カルチノイドの1例に対して気管支鏡下切除を施行したので報告する. 症例. 75歳, 男性. 主訴は労作時呼吸困難気管支鏡検査で左上幹入口部に直径約8mmの広基性病変を認め, 生検にて定型的カルチノイドと診断された. 外科的切除術を勧めたが本人から手術の同意が得られなかった. そこで, 腫瘍残存の可能性がある治療法であることを本人に十分説明し理解してもらった上で, 気管支鏡下に腫瘍切除を施行した. まず高周波スネアによる腫瘍切除を行い, さらに遺残した腫瘍を二期的に半導体レーザーにて焼灼した.治療部位はその後, 約4年6カ月の経過観察で局所再発を認めない. 結論. 気管支鏡下切除は今後腔内型定型的気管支カルチノイドの治療法の選択肢の一つとなる可能性が示唆された.